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排序方式: 共有1186条查询结果,搜索用时 15 毫秒
131.
Smad-mediated regulation of microRNA biosynthesis 总被引:1,自引:0,他引:1
132.
Fujii S Fukamachi K Tsuda H Ito K Ito Y Ochiai A 《Biochemical and biophysical research communications》2012,417(3):1074-1079
The neoplastic transformation by mutant RAS is thought to require remodeling of expression of an entire set of genes. However, the underlying mechanism for initiation of gene expression remodeling in tumorigenesis remains elusive. This study was aimed to define the oncogenic role of EZH2, a histone modifier protein that is induced by oncogenic mutant RAS, using pancreatic cancers of transgenic rats exogenously expressing human mutant RAS. Immunohistochemical observation of preneoplastic or cancerous lesions in the animal model suggested that upregulation of Ezh2 protein is an initiating event in pancreatic carcinogenesis. MEK-inhibition or Elk-1-knockdown downregulated EZH2, and MEK-inhibition or EZH2-knockdown restored expression of a tumor suppressor, RUNX3 in human and rat pancreatic cancer cells activated by the oncogenic RAS. Furthermore, Elk-1- or EZH2-knockdown inhibited growth of the cancer cells. These results strongly suggested that the oncogenic RAS upregulates EZH2 through MEK-ERK signaling, resulted in downregulation of tumor suppressors including RUNX3 in pancreatic carcinogenesis. 相似文献
133.
Tamio Ohno Keiko Hata Taisuke Baba Fusayo Io Misato Kobayashi Fumihiko Horio Masahiko Nishimura 《Mammalian genome》2012,23(11-12):764-769
Consomic strains, in which one chromosome is derived from a donor strain and the other chromosomes are derived from the recipient strain, provide a powerful tool for the dissection of complex genetic traits. In this study we established ten consomic strains (A-2SM, A-6SM, A-11SM, A-12SM, A-13SM, A-15SM, A-17SM, A-18SM, A-19SM, A-YSM) using the SM/J strain as the donor and the A/J strain as the recipient; these are the parental strains of a set of SMXA recombinant inbred (RI) strains that we had developed previously. We analyzed body weights and blood lipid levels in the consomic and parental strains. The mean values for each trait showed a continuous range of variation in the consomic strains suggesting that they are controlled by multiple genes. We previously identified suggestive QTLs for body weight on chromosome 6 in SMXA RI strains and (SM/J?×?A/J)F2 mice. The observation that the A-6SM consomic strain had a significantly lower mean body weight than the A/J strain supports the presence of this QTL on chromosome 6. Similarly, the higher blood triglyceride level in the A-11SM strain shows the existence of a previously mapped QTL on chromosome 11, and the A-12SM strain provides evidence of a QTL for blood total cholesterol level on chromosome 12. These consomic strains, along with the previously developed set of SMXA RI strains from A/J and SM/J mice, offer an invaluable and powerful resource for the analysis of complex genetic traits in mice. 相似文献
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Eguchi K Manabe I Oishi-Tanaka Y Ohsugi M Kono N Ogata F Yagi N Ohto U Kimoto M Miyake K Tobe K Arai H Kadowaki T Nagai R 《Cell metabolism》2012,15(4):518-533
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138.
Koyama S Hata S Witt CC Ono Y Lerche S Ojima K Chiba T Doi N Kitamura F Tanaka K Abe K Witt SH Rybin V Gasch A Franz T Labeit S Sorimachi H 《Journal of molecular biology》2008,376(5):1224-1236
During pathophysiological muscle wasting, a family of ubiquitin ligases, including muscle RING-finger protein-1 (MuRF1), has been proposed to trigger muscle protein degradation via ubiquitination. Here, we characterized skeletal muscles from wild-type (WT) and MuRF1 knockout (KO) mice under amino acid (AA) deprivation as a model for physiological protein degradation, where skeletal muscles altruistically waste themselves to provide AAs to other organs. When WT and MuRF1 KO mice were fed a diet lacking AA, MuRF1 KO mice were less susceptible to muscle wasting, for both myocardium and skeletal muscles. Under AA depletion, WT mice had reduced muscle protein synthesis, while MuRF1 KO mice maintained nonphysiologically elevated levels of skeletal muscle protein de novo synthesis. Consistent with a role of MuRF1 for muscle protein turnover during starvation, the concentrations of essential AAs, especially branched-chain AAs, in the blood plasma significantly decreased in MuRF1 KO mice under AA deprivation. To clarify the molecular roles of MuRF1 for muscle metabolism during wasting, we searched for MuRF1-associated proteins using pull-down assays and mass spectrometry. Muscle-type creatine kinase (M-CK), an essential enzyme for energy metabolism, was identified among the interacting proteins. Coexpression studies revealed that M-CK interacts with the central regions of MuRF1 including its B-box domain and that MuRF1 ubiquitinates M-CK, which triggers the degradation of M-CK via proteasomes. Consistent with MuRF1's role of adjusting CK activities in skeletal muscles by regulating its turnover in vivo, we found that CK levels were significantly higher in the MuRF1 KO mice than in WT mice. Glucocorticoid modulatory element binding protein-1 and 3-hydroxyisobutyrate dehydrogenase, previously identified as potential MuRF1-interacting proteins, were also ubiquitinated MuRF1-dependently. Taken together, these data suggest that, in a multifaceted manner, MuRF1 participates in the regulation of AA metabolism, including the control of free AAs and their supply to other organs under catabolic conditions, and in the regulation of ATP synthesis under metabolic-stress conditions where MuRF1 expression is induced. 相似文献
139.
LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 expression in human lymphatic endothelium. 总被引:2,自引:0,他引:2
Yoshihiko Sawa Takeshi Ueki Minoru Hata Kana Iwasawa Eichi Tsuruga Hiroshi Kojima Hiroyuki Ishikawa Shigemitsu Yoshida 《The journal of histochemistry and cytochemistry》2008,56(2):97-109
We have previously reported the TLR4 expression in human intestinal lymphatic vessels. In the study here, microarray analysis showed the expression of the TLR4, MD-2, CD14, MyD88, TIRAP, TRAM, IRAK1, and TRAF6 genes in cultured human neonatal dermal lymphatic microvascular endothelial cells (LEC). The microarray analysis also showed that LEC expressed genes of IL-6, IL-8, VCAM-1, and ICAM-1, and the real-time quantitative PCR analysis showed that mRNA production was increased by lipopolysaccharide (LPS). The LPS-induced IL-6, IL-8, VCAM-1, and ICAM-1 production in LEC was suppressed by the introduction of TLR4-specific small interfering RNA, and also by anti-TLR4, nobiletin, and CAPE pretreatment. These findings suggest that LEC has TLR4-mediated LPS recognition mechanisms that involve at least activation of NF-kappaB, resulting in increased expression of IL-6, IL-8, VCAM-1, and ICAM-1. Both the LPS effect on the gene expression and also the suppression by nobiletin and CAPE pretreatment on the protein production were larger in IL-6 and in VCAM-1 than in IL-8 and in ICAM-1 in LEC. The signal transduction of NF-kappaB and AP-1-dependent pathway may be more critical for the expression of IL-6 and VCAM-1 than that of IL-8 and ICAM-1 in LEC. 相似文献